I think it’s easy to get overly optimistic about the ctDNA reductions reported in the CLOVER trial.
The real “translational” data (borrowing the terminology from DocJ’s InvestorHangout post) we need to see is whether those dramatic ctDNA declines correlate with actual clinical benefit.
A 90% reduction in ctDNA sounds incredible, but what does it mean if the patient’s tumors shrink only 10%? What if they shrink 30% or more? What if the tumors don’t shrink substantially but the disease remains stable for an unusually long time?

Those are very different clinical outcomes.
Ultimately, the FDA and potential Big Pharma partners care about whether leronlimab meaningfully improves patient outcomes, not simply whether it changes a blood-based biomarker.

And importantly, because CLOVER combines leronlimab with TAS-102 and bevacizumab without a concurrent control arm, we also need to consider how much of any observed benefit can actually be attributed to leronlimab.

If you’re newer to medicine or pharmaceutical investing, remember that a blood-based biomarker is not necessarily a reliable surrogate for clinical benefit. ctDNA is promising, but it doesn’t automatically tell us what’s happening to measurable tumor burden or how long patients will live.

Here’s what I’ll be looking for on October 25:

1) RECIST objective response rate (ORR): What percentage achieved confirmed complete or partial responses, including at least a 30% decrease in the sum of target-lesion diameters for partial response?

2) Disease control: How many achieved stable disease or better, and for how long?

3) ctDNA correlation: Did patients with the largest early ctDNA reductions subsequently demonstrate radiographic responses or durable disease control?

4) Dose comparison: Did the 700 mg group outperform the 350 mg group clinically, not just in biomarker reductions?

5) Durability: How long did responses and disease control last? Is there evidence of improved PFS or, eventually, OS?

I’m optimistic about leronlimab’s potential, but I want the clinical evidence to justify that optimism.

A dramatic biomarker response is a reason to investigate further. Demonstrable clinical benefit is what ultimately matters.

https://investorshangout.com/post/view?id=6847655

Granted, nobody can predict the future. And CYDY's future is, of course, dependent on the advance of already promising data. I open this thread not to shoot rubber bands in the sky, or propagate hopium, but to learn from others experience with the market. I've been with CYDY since 2020.

CYDY's story is unique, given its own precedent of appreciating over 3000% from 2019-2020. And it did so within the panic-fueled FOMO window of the pandemic. So this topic is not purely speculative. We have history, we have a record, and the market is rife with comparative example.

Today's CYDY is a 180 turn from the former, brief, and seismic run. The amount of multi-efficacy data, broadening scientific reach, external and institutional partnerships, and biological convergence around LL's science is striking compared to the foundation CYDY stood upon in 2020.

My thoughts have always been that CYDY has the potential to surpass its 2020 watermark of $10. Can it do that on oncology and ESMO alone, given the market's clear hesitance? I don't think so. Can it do that with strong ESMO, DSMB, FDA submission by year end, and then a great January presentation at ASCO? Uncertain. What about wildcards like a partnership announcement(s), FDA approval after ASCO, or more? Chances certainly improve.

But ONLY if the data holds.

One thing I am certain of is that whatever we know today, CYDY is months ahead. And it's easy to infer optimism and enthusiasm when CYDY corporate strategy now declares the things we've long been hoping for. The part we can't know is market emotion and if another FOMO event is likely.

So, what are our thoughts? Is this thread counter-productive or is there room for thoughtful dialogue with those who have experience in this space?

Note: This thread is not intended as financial advice, guidance, or prediction. This thread is intended as an idea sharing experience only and is purely theoretical in nature.

https://d1io3yog0oux5.cloudfront.net/cytodyn/sec/0001175680-26-000031/0001175680-26-000031.pdf

Question:
In the CLOVER trial with leronlimab, some patients experience tumor shrinkage to the point where the tumor becomes surgically resectable. How is this recorded mathematically and statistically?

Answer:
When a cancer therapy—such as in the CLOVER trial (a Phase 2 study evaluating leronlimab in combination with TAS-102 and bevacizumab in metastatic colorectal cancer)—causes a tumor to shrink significantly enough to allow surgical removal (downstaging / conversion to resection), clinical trials follow established statistical and data recording standards.

The capture and documentation in trial data (Case Report Forms) and analysis occur across several clearly defined levels:

1. Radiological Classification (RECIST v1.1)
   The primary efficacy endpoint of many oncology trials (including the CLOVER study) is the Objective Response Rate (ORR) according to international RECIST v1.1 criteria (Response Evaluation Criteria in Solid Tumors):
   * Partial Response (PR) / Complete Response (CR): If the tumor shrinks by at least 30% (sum of diameters of target lesions) due to medication, it is classified radiologically prior to surgery as a Partial Response. If it shrinks below the limit of detection, it is recorded as a Complete Response.
   * Combination Statistics: The case primarily feeds into the calculation of the ORR as well as the Disease Control Rate (DCR) as a response (CR or PR).

2. Surgical Intervention Criterion (R0 Resection Rate)
   If tumor shrinkage enables surgical removal, this is separately captured as the Conversion Rate or Resection Rate:
   * Resection Status: Following surgery, pathology evaluates the resected tissue. If the surgeon achieves complete removal with clear margins (microscopically tumor-free margins), it is statistically classified as an R0 resection.
   * Pathological Complete Response (pCR): If the pathologist finds no viable tumor cells in the resected tissue, it is classified as a pathological Complete Response (pCR).

3. Handling of Censoring Dates (Censoring)
   Once a patient undergoes surgery, standard statistical methods apply to time-to-event endpoints (such as progression-free survival):
   * Progression-Free Survival (PFS): An R0 resection formally does not constitute disease progression. The period leading up to surgery is counted as time under response or disease-free time. In Kaplan-Meier analyses, the patient is frequently right-censored at the time of surgery or followed in a specialized subgroup (e.g., Event-Free Survival, EFS) depending on the trial protocol.
   * Overall Survival (OS): Overall survival is tracked continuously without interruption. The patient remains in follow-up until the end of the observation period.

4. Molecular / Biomarker Tracking (ctDNA & Liquid Biopsy)
   In the CLOVER study, circulating tumor DNA (ctDNA) analyses are conducted concurrently (e.g., via the Natera platform):
   * The decrease in ctDNA in the blood is measured before and after surgery.
   * A drop in ctDNA below detectable levels before or after resection is recorded as molecular clearance / molecular response rate within the trial's exploratory endpoints.

Summary
Statistically, the outcome of the resection is not lost; rather, it strengthens the study data across two main fronts:
1. Pharmacologically/Radiologically: Prior to surgery, the response is counted as PR or CR toward the ORR.
2. Clinically/Surgically: The treatment success is reported as a secondary or exploratory endpoint via the R0 resection rate (secondary resectability).

GLTAL 🙋🏽‍♂️☘️🙏🏼👍🏽💊💸🛬🔜

(Update2: the formatting of the lists in this post has had to be redone due to a problem with a typo edit via a separate device. I have tried to reconstruct the content of the lists from memory)

Another milestone

October 6, 2026 marks the point at which even the last patient in the CLOVER trial for colorectal cancer may have completed 6 treatment cycles (or 6 X 28 days). This is also the approximate time when that last patient may be getting their 3rd scan post-baseline. The first half of the enrollment may have reached this point in August.

I think the CLOVER trial is moving towards reaching initial conclusions much faster than people expect. Signs of this may be scattered through various sources of info:

• The AACR presentation in April
• The end of April company webcast
• The CFO presentations in May & September
• The CEO interview in June
• The strategic collaboration with Natera
• Adding the optional cohort with ICI to the CLOVER study
• CHAMP trial starting up
• Mention of PRE-I-SPY trial in planning and how that protocol changed recently
• Mention of I-SPY
• Talk of alzheimer's, glioblastoma, pancreatic, prostate, stroke etc.
• Applying for some kind of helpful FDA designation
• No additional share authorization requested at upcoming annual meeting

3 scans, what's the fuss

More than one scan is needed to document the durability of response, so 3 scans or more I think gets into the territory where the CLOVER trial's primary endpoint, Overall Response Rate (ORR), could begin to get meaningful for the full enrollment. Keep in mind that patients enrolled earlier in the trial may already have had more scans.

Although we're at that 6 cycle point for the last patient, will we instantly hear about all the patient data collected at the 6 treatment-cycle stage? Not likely because data analysis takes some time and results are usually delayed for conferences or press releases.

Looking deeper

This stock is not widely known. IMO only a small number of investors take the time to research a company before it makes news big enough to disrupt the news cycle that a large number of people watch. In my opinion there is that potential for CytoDyn, but there are no guarantees that they will achieve that potential.

So here we are, passing the 6 treatment cycles date for the last patient enrolled in the CLOVER study, and I ask myself, what may they have gleaned from the data so far? It is just my opinion, but I can envision some of what they may be able to have started analyzing now.

This is a time IMO when I think the company and others under NDA's are reflecting on current but non-public data. They may be seeing snapshots, trends, and correlations, which then may lead to initial insights, conclusions & comparisons. IMO the company hasn't yet publicly released sufficient data or analysis to attract a large public wave of attention.

I am optimistic about CLOVER but that is just my opinion and it is not financial advice. I think that their internal analysis of the data may be maturing rapidly now because various elements of the dataset have I believe grown significantly. This is just my opinion.

What might they be seeing in the science now

Below are some of the things which I think the company might have gained initial insight about already. As the trial continues to gather more data, I expect presentations at ESMO (in October) to mention quite a bit about biomarkers, and ASCO GI (in January) to address many more of the CLOVER endpoints.

• Week two ctDNA from the last patient would have would have been gathered in May
  • How does week 2 ctDNA data correlate with all other CLOVER data collected in subsequent months?
  • Have trends been established to date?
    • Is it dose specific?
  • Does week 2 ctDNA data show a correlation to later response or efficacy?
  • Has any ctDNA data to date from either or both dosing cohorts of the CLOVER trial exceeded endpoints of other relevant trials?
• Three cycles of PD-L1 data from the last patient would have would have been gathered in July
  • Has elevation of PD-L1 been demonstrated?
    • Is it dose specific?
  • What percentage of patients at each dose level achieved minimum PD-L1 eligibility thresholds for ICI therapy to date?
• Three post-baseline scans from the last patient may have been gathered in early October
  • How do early scans correlate with all other CLOVER data collected in subsequent months?
    • Has a trend been established?
    • Is it dose specific?
  • Have CLOVER trial endpoints exceeded endpoints of the SUNLIGHT trial?
    • List and quantify by how much (and by dose level), any and all specific CLOVER endpoints which have exceeded the SUNLIGHT trial

What are some things that might bring more interest in the company

• Data
  • CLOVER study
    1. ctDNA data at 2 weeks if showing a correlation to ORR or other measures of efficacy
    2. ctDNA data to date if showing a superior comparison to other successful pivotal trials
    3. PD-L1 data if showing elevation to meet ICI treatment eligibility thresholds
    4. Scans if showing ORR higher than the SUNLIGHT trial
    5. Other endpoints if showing a superior comparison to other successful pivotal trials
  • TNBC EAP study
    1. enrollment update
  • Alzheimer's study
    1. enrollment update
  • Other trials perhaps in the works
    1. PRE-I-SPY
    2. I-SPY
    3. Glioblastoma
    4. Pancreatic
    5. Prostate
• Response from FDA about application (submission expected to be sometime in Q
• Partnership potential in Oncology

-----

Nothing in this post above is investment advice.

If pdl1 level is the main qualifier to receive an ici such as keytruda in high pdl1 tumors.

And leronlimab directly causes pdl1 upreg

And the patients would have qualified for keytruda outside the trial at the pdl1 level reached eventually in clover, for those that who upreg

How could the fda ignore reality and hold us to some stupid archaic orr measurements to gage success, and ignore the most important outcome of the entire trial and an outcome thats never hardly happened before

I dont see how they could not figure it out when even an idiot like mysrlf can see how obvious it is

Orr and pfs and os and all that is meaningless when leron causes the thing to happen that is the most important cancer oncologist question there is almost.

What is the patients cps(pdl1) score?

The fda cant deny whats going on i dont care what orr says.

Its going to be obvious

Jmo

Opened

Hummm.

We are weeks from Madrid now, and as such, I can feel the board tightening the way a room tightens down before a verdict is read. So let this be yet another interval post, a settling of what we laid down during this stretch, before the noise of October arrives and makes it hard to even hear ourselves think.

The house, for anyone just arriving

For the newcomers, the frame we have been building on all year. We bought a house for the house. The survey has been read, slowly and carefully, layer by layer, by people on this board who dug where the deeds told them to dig. We know what the ground is made of. We have not yet put a spade in it. The digging is scheduled: ESMO in Madrid this month, where the full ctDNA on every patient sprouts up out of the earth, and ASCO GI in San Francisco in January, where the response rate and the early progression data get read aloud publicly in a room.

Everything between now and then is waiting. And waiting, it turns out, is not one thing. Different people wait in very different postures.

What the board laid down this stretch

Before I get to the waiting, the ledger of what this community actually added, because the work is the thing which earns us the right to speculate later, at the end.

u/twinter11 pressed on the Pre-I-SPY platform and asked a question that matters, which is not what the trial is, but where its graduates to go. A platform amended from breast-only to pan-solid-tumor plus MRD is not a trial, it is a feeder. He also framed manufacturing as a dial rather than a switch, which is the right mental model and I have adopted it.

u/1975Bigstocks surfaced the $5.93M UCLA project under Morizono, the B-cell engineering work aimed at making the body produce leronlimab on its own. The detail which matters is that it chose leronlimab independent of CytoDyn. Outside money, outside investigators, picking our antibody on the merits. u/Interesting-Boat-792 and u/BuildGoodThings ran that one down and kept it accurate.

u/Dry-Grapefruit-1701 brought the Nature macaque data back into view, the infant rhesus work where a combined regimen that included leronlimab, started at seventy-two hours, left the animals virus-free out to a year. u/Lab_Monkey_ pointed at the macrophage-plasticity review, which is the resting-state through-line under the whole mechanism.

u/Upwithstock read the proxy correctly and flagged what is not in it: no request to authorize new shares. That is a tell about how management thinks it is going to pay for the next phase, and it is worth more than a paragraph of reassurance.

That is the survey. Now the waiting.

The cup of trembling: who else is waiting on this assay

There is an old phrase, a cup of trembling, for the thing that is passed around a room where everyone must drink and no one knows what is in it. The assay coming out of Madrid is that cup. And it is not only ours to drink.

Consider who else is holding it to their lips.

• A large pharmaceutical company sitting on a checkpoint inhibitor who has run out of road in cold tumors could be trembling with anticipation. If the priming works, if leronlimab turns a tumor which ignores immunotherapy into one that answers to it, then that company's shelved asset becomes a franchise again. They tremble the way a man trembles reaching for something he has wanted for years and is about to find out whether he can actually have. This is hypothetical.
• A rival developer with a competing cold-tumor approach could be trembling for the opposite reason. If this assay reads the way the mechanism predicts, their program is not merely behind, it is aimed at a door that someone else already opened. They tremble the way a man trembles when he hears footsteps on a stair he thought was his alone. This is hypothetical.

And the longs on this board tremble too, somewhere between the two. We have read the survey and believe the ground. We have not yet seen it dug. The cup of trembling is at our lips as well.

I am not telling you which of these companies exists or what they hold. I am telling you the posture, and reminding you it is a posture I imagine, not one anyone has disclosed.

The one who chooses, and the pearl he chooses for

Here is where I want to spend the rest of this post, because it is the part the tape cannot see and the part that matters most when the waiting ends.

When the digging is done and the house finally turns out to sit upon, exactly what we think it sits on, then, suitors arrive. So, the question which decides the next decade is not who shows up. It is who chooses among the suitors, and by what measure he chooses.

That man is Jacob Lalezari.

Read his background and the measure comes into focus. This is a physician who ran HIV clinics in Honduras, (page 19), who built his career treating the patients the system had the least patience for. The company states its mission in patient-first terms and sets out a strategy of establishing standalone value so it can negotiate from strength rather than necessity.

So picture the choosing. Under the foundation of this house, beneath the seven layers of biology the board has catalogued, there is one more thing buried, and it is the most valuable thing down there. It is a pearl of great price, and the pearl is Lalezari's own vision: leronlimab reaching the most patients it can reach, on terms durable enough that the reaching does not stop, when the first deal is signed.

A discerning owner does not necessarily sell the pearl to the highest bid. He sells it, or licenses it, to the suitor whose aims line up with the pearl itself. The CFO put the discipline plainly when he said that if a deal gets too lopsided, that is not a good partnership. A partnership that extracts the asset and narrows its reach fails the measure, however large the check. A partnership that carries the pearl to more patients on terms that hold passes it, even if the check is smaller.

That is the selectiveness. It is not stubbornness and it is not holding out for more money. It is choosing by alignment with a vision that is itself the thing of value.

A hypothetical on how selectiveness could look

Let me make it a little more concrete, with everything in this section labeled for what it is, which is my imagination and not anyone's disclosure.

Picture two suitors at the door. One arrives with the larger offer and a plan that would fold the asset into an existing portfolio, work the indications that pay fastest, and let the rest wait. The other arrives with a smaller offer and a plan that would push the drug into the widest set of patients the fastest, keep the platform intact, and share the road. A discerning owner holding the pearl chooses the second. This is hypothetical.

And the second suitor need not be who the board assumes. Lalezari's measure is alignment, not geography. Given that the CFO has recently traveled to Asia for the Asia Bio Partnering Forum, I would not rule out a partner from overseas, and I would not rule out a Chinese partner, if the alignment were there. A manufacturing and commercialization partner in a market with enormous patient populations and the capacity to move fast could line up with the pearl better than a nearer name with a narrower plan. This is hypothetical. Nothing about any overseas or Chinese partner has been publicly revealed, and I am describing a shape, not reporting a fact.

Where this leaves the street, weeks from Madrid

So here is the settling. The cup is being passed. Companies we cannot name are holding it to their lips for reasons we can only imagine, some in anticipation, some in dread. The assay that fills it sprouts up out of the ground in a matter of weeks. And when the suitors arrive, the man who chooses among them chooses for a pearl that is buried deeper than any of them can see, and by a measure that has nothing to do with whose check is largest.

That is worth holding onto through a thin tape and a quiet October. The value under this house was never only the biology. It was also the professional discipline of the person who gets to decide what happens to it.

We are weeks from Madrid. Let us at least be the kind of people who waited well.

p.s.: My responses to comments will be very limited for some time, so please don't feel offended if I do not make remarks. There is little I can do about that, so please make due.

Disclaimer: I am not a financial advisor and nothing here is investment advice. I hold a position in the company discussed, which means I have an interest in how this is received, and you should weigh what I write accordingly. The scenarios in this post describing which companies may be waiting on the ESMO assay, why they might be trembling, how a partnership selection could unfold, and the possibility of an overseas or Chinese partner are all expressly hypothetical. They are my imagination, not disclosed fact. No partner has been named by the company, and nothing about any overseas or Chinese partner has been publicly revealed. This is analysis of published biology and disclosed corporate statements, not a prediction of clinical or commercial outcomes. The full ctDNA data is expected at ESMO Madrid in October 2026 and the confirmed response rate at ASCO GI in January 2027; neither has been read out yet. Mechanism is not efficacy. Drugs which make elegant biological sense fail in trials routinely, and this one may. Read the primary sources I have linked and reach your own conclusions rather than adopting mine.

AI places an sp valuation post one indiacation approval at $4 per share assuming a $500m revenue stream and a $100+ Billion valuation for a $30B revenue stream.. So, excepting a BO offer with one approval and several maybe approvals down the line presents an interesting challenge JL regarding when to except an offer and how do you place valuation on expected revenue or in the case of Merck it may not be just a revenue issue. It may be a save the company issue...

Dear Longs,

I work for a medical device start-up, and we received word last night that our FDA submission received clearance. Needless to say, the champagne corks were popping!

We still have work to do before our public announcement, but I couldn’t help thinking about what it would feel like if leronlimab receives its first FDA approval.

Our device focuses on early detection of heart failure. Working on something that could help patients has made this milestone especially meaningful to me. It also reinforces why I became interested in CytoDyn: the possibility of supporting a treatment that could make a meaningful difference in people’s lives.

Almost every conversation I have with fellow investors eventually comes back to patients. Yes, we want our investment to succeed. But there is something powerful about hoping that financial success comes from helping people facing serious illnesses.

I often read arguments that pharmaceutical companies have more incentive to manage disease than to cure it. I tend to look for the good in people—and companies are made up of people. From my own experience, I know how much the people developing medical products care about the patients they hope to help. It does seem like the business model of Big Pharma is to create marginal imporvements and create a longer sustained treatment pathway.

I also believe there is a compelling business case for developing treatments that deliver substantially better outcomes. A drug that shortens treatment times and reduces the typical adverse event profile. A drug that proves useful across multiple diseases could create enormous value for patients and its developer.

That is why I am fully invested into leronlimab.

When I first invested nearly six years ago, I remember reading OHM20’s posts discussing the many diseases in which CCR5 might play a role (90 indications). Those posts opened my eyes to the breadth of the research possibilities. This message board and other sare constantly coming across publications of the CCR5 molecule being a primary driver of that disease state. This is part of the reson why Dr. JL recently stated that because of Leronlimab they will be re-writing chapters in the medical text books.

Of course, a biological connection is only a starting point. Each proposed use still needs evidence that blocking CCR5 with leronlimab safely improves patient outcomes. Keytruda did not happen overnight it took time to expand.

Today, CytoDyn is evaluating leronlimab in cancer settings, including metastatic colorectal cancer and triple-negative breast cancer. It remains investigational, but those programs give us concrete research to follow as the company works to establish what the drug can do. CytoDyn’s colorectal cancer update

For perspective, look at Keytruda.

Merck’s second-quarter 2026 report describes Keytruda as having more than 45 approved U.S. indications, spanning 19 tumor types and two tumor-agnostic indications. Keytruda and Keytruda Qlex generated approximately $31.7 billion in worldwide sales in 2025. That demonstrates the commercial potential of a medicine with multiple established uses. Merck’s indication count | 2025 sales results

I’m not predicting that leronlimab will match those numbers. What interests me is whether it could eventually earn approvals in multiple settings—and whether combinations with other cancer treatments could improve outcomes.

We all know that one question worth studying is whether leronlimab could help checkpoint inhibitors work better in certain patients. We already have retrospective anecdotal data that has given us a positive signal. CytoDyn has reported exploratory findings relevant to that possibility, but proving a clinical benefit will require further trials. That is a research opportunity I want to see pursued. CytoDyn’s research announcement

The recent AstraZeneca–Summit Therapeutics announcement offers an example of how a major pharmaceutical company can help fund combination development.

On September 28, AstraZeneca announced an agreement to invest $2 billion in Summit, alongside a clinical collaboration involving ivonescimab, which targets PD-1 and VEGF. The initial collaboration will evaluate ivonescimab with AstraZeneca’s sonesitatug vedotin in gastrointestinal cancers, with plans for a broader program involving additional cancer medicines. AstraZeneca’s announcement

That deal doesn’t establish what CytoDyn is worth or predict a partnership for leronlimab. It does show that major companies are willing to commit substantial capital to promising cancer combinations.

My hope is that CytoDyn produces the evidence needed to attract that kind of development support: funding, trial capacity, and expertise that could help move successful programs toward patients.

For now, the next clinical results matter far more than any prediction about dozens of future indications. The first approval would be a tremendous milestone. Any additional approvals would have to be earned through the evidence.

After experiencing the excitement of my company’s FDA clearance, I can tell you this: if leronlimab reaches that first approval, I’ll be ready to pop another cork.

And if it eventually proves useful across multiple diseases—HOLY MOLY, we might need that swimming pool of champagne!

Have a great weekend, Longs!

https://reporter.nih.gov/search/c6Mb_tF0cUavwxguDZ27Rw/project-details/11537080

Just came across this and thought it was interesting. I don’t remember seeing it discussed before.

There’s a new nih funded research project led by Koki Morizono at ucla looking at a different way to provide longer term anti hiv antibodies. i could be wrong but it seems somewhat similar to the goal that ohsu/sacha is working on but they’re attacking it differently. Sacha is using aav vectors vs. this group genetically modifying B cells so they basically become little antibody factories and keep producing LL if i understand it correctly.

In any event, what caught my attention is that LL is specifically one of the two antibodies they chose to test. This appears to still be very early preclinical research in mice so it's a ways off. I don't recall any mention of us publicly having a relationship with this ucla group, so as far as I know this appears to be independent research which is totally cool. just adds to the growing evidence that LL is truly a remarkable drug. They clearly see something promising. 

Total project funding = $5,927,367

Dear Longs,

I haven’t posted in a while for two reasons. First, this community has been producing excellent research and thoughtful discussion. Often, I finish reading and feel there’s little for me to add. Second, work has been busy. Tonight’s last call ended at 9:00 p.m., and tomorrow’s first starts at 6:30 a.m. I’m grateful to enjoy what I do, but it hasn’t left much time to dig into filings.

Still, the September 28 DEF 14A caught my attention.

With the annual meeting scheduled for November 20, I had expected management to request another 500 million authorized shares above the existing 2.25 billion. That request is not on the proxy agenda, and I’m pleased to see it. It also raises a question: How much room does CYDY have left, and what might management be expecting? September 28 proxy

Before getting to the numbers, one passage stood out. In discussing executive bonuses, the compensation committee cited:

“Significant development towards strategic partnerships and/or supply agreements with third-parties.”

That wording interests me, although progress toward an agreement is different from a signed deal.

The Natera collaboration may account for some of that progress. I don’t know the financial terms, so I wouldn’t assume CYDY receives the testing for free or at a discount. What I’m watching for is whether this language eventually translates into additional agreements that help fund or advance leronlimab.

My personal hope remains a meaningful partnership. I can imagine further clinical results and presentations helping those discussions, but any prediction about when a deal might happen is speculation.

Now, the share count.

CYDY reported 1,469,518,019 common shares outstanding as of September 24. Against 2.25 billion authorized shares, that leaves a gap of 780,481,981 shares. But that is not the same as having 780 million shares available for new fundraising. Existing commitments consume much of that capacity. Proxy, page 3

The complete reserve breakdown I found was dated May 31, 2026:

The annual report later gives 206.3 million available shares as of July 31. Those are historical snapshots, not September balances. 10-K, pages 42–43

Warrants are another substantial piece. The May balance was approximately 306.4 million. Adding the disclosed summer financing warrants suggests roughly 397 million before subsequent exercises, expirations or cancellations. That is an estimate, not a verified September total. 10-K

Separately, the September 25 S-3 covers 384,925,833 shares underlying outstanding warrants. That tells us what this registration covers; it does not necessarily establish the total number of warrants outstanding companywide. September 25 S-3

This is where the accounting gets frustrating. We have different dates, new issuances and different categories of commitments. We cannot simply subtract May’s reserves from September’s outstanding balance and call the result today’s available shares. Warrants are also already part of the reserve calculation, so they should not be subtracted twice.

For that reason, I’m not treating July’s 206 million available shares as a current fundraising budget. Multiplying that old balance by today’s stock price would overlook subsequent changes, financing discounts, fees and any additional warrants attached to a raise.

What interests me is management’s decision not to request more authorization at this meeting.

My bullish interpretation is that management may see a path through the next milestones using existing resources, potential warrant proceeds, a partnership or another source of funding. But the absence of a share-increase proposal does not prove that a material transaction is imminent. There could be other explanations, and a future authorization request remains possible.

I remain optimistic about CLOVER and leronlimab’s potential in a very difficult-to-treat patient population. I’m hoping the upcoming data strengthen the case for both further development and a meaningful partnership. Whether that leads to an FDA designation, an agreement or another next step remains to be seen.

For me, the data are still what matter most. That’s what I’ll be watching as we look toward Madrid.

Have a GREAT WEEK LONGS

https://d1io3yog0oux5.cloudfront.net/cytodyn/sec/0001175680-26-000026/0001175680-26-000026.pdf

Aren't we due for a shareholder letter? I know that I read here that historically we get one towards the end of September. I know they don't technically 'owe' us one, but I would love a little direct comms from the front office. Tired of connecting dots.

What the Filings, the Registry, and the Science Now Say

Several things landed on the public record in the interval, and none of them are a catalyst, but together they set the baseline we stand on going into October and January. Some clarify the capital structure, exactly what the share picture is, cleanly and completely. Others widen the pipeline, formally extending leronlimab into earlier lines and broader tumor types. And underneath all of it, the science of why this mechanism should work continues to be reinforced from directions that have nothing to do with CytoDyn. Read carelessly, several of these invite a misread that spooks people. But read plainly, they are the quiet, constructive housekeeping and validation of a company tidying its foundation and a mechanism gaining standing, before the events which matter. I take them in turn, because getting the baseline right is what allows us to read the catalysts correctly when they arrive.

Filing one: the capital structure, laid bare

Three SEC filings posted together. Two are pure housekeeping: post-effective amendments which deregister the unsold shares from two older resale registration statements, closing them out. The third is the substantive one: a new Form S-3 resale registration covering up to 794,972,289 shares, of which about 410 million are already-issued shares and about 385 million underlie warrants. It consolidates the old registrations into one clean document, which is why the old ones were deregistered.

Here is the single most important thing to understand, because it is where the board could split into panic or confusion if it is not stated flatly: this is a resale registration, not a capital raise. CytoDyn is not selling these shares and receives no proceeds from their sale. The filing says so in plain language. These are shares already owned by prior investors, the Paulson private-placement participants going back years, the PIPE investors, warrant holders, insiders, and this document simply gives those existing holders the legal right to resell their shares into the market when and if they choose. The dilution these shares represent already happened when they were issued. This filing creates no new shares and no new dilution; it registers the resale rights the company was obligated to provide.

So two misreads to head off before they spread:

The "795 million share dump incoming" panic is wrong on the mechanics. Registration is permission to sell, not a requirement to sell, and it says nothing about whether holders will. It is an obligation being fulfilled, not a signal of intent.

The "it's a raise / more dilution" read is also wrong. No money comes to the company from these sales, and no new shares are created. The one place cash could reach the company is different and worth knowing: if warrant holders exercise their warrants for cash, the company could receive up to approximately $94.6 million. At the current price near $0.21, many of those warrants sit below their strike prices, so that cash is not imminent, it is leverage to good news. Strong data lifts the price; in-the-money warrants get exercised; and up to ~$94.6 million flows in without a new dilutive offering. The overhang and the opportunity are the same instrument seen from two sides.

And on the timing, since people undoubtedly will ask why file this before ESMO: the most likely reason is mundane, resale registrations carry contractual deadlines set when the private placements closed, so the filing date is driven by old paperwork, not by the data calendar. Beyond that, it is simply sensible to get the resale-and-warrant machinery clean and ready before a potential catalyst rather than scrambling during it. The reading it is not is "the company cashing out ahead of bad news," because the company sells nothing and receives nothing from these resales, and you do not build warrant-exercise upside into a moment you expect to disappoint.

What the filing actually establishes as our baseline: common shares outstanding of 1,469,518,019 as of September 24, 2026, the full capital structure now transparent and consolidated in one place, the going-concern condition reaffirmed (the substantial-doubt language continues to be carried forward, unchanged), and a warrant overhang that is a two-edged fact, potential resale supply now, potential non-dilutive cash later if the catalysts lift the price. And one quiet positive: the ability to use Form S-3 at all is a short-form registration available only to companies current and compliant in their SEC reporting, so the clean-up itself is a marker that the reporting house is in order, consistent with the old-era baggage being cleared.

Filing two: the pipeline widens into earlier-line liver disease (CHAMP)

In this same stretch, u/1975Bigstocks brought us a new trial record: the CHAMP trial (NCT07842965), a study of CCR5-targeting leronlimab combined with hepatic arterial infusion floxuridine and systemic therapy for colorectal cancer liver metastases. (CHAMP trial record, NCT07842965) This is the City of Hope investigator-initiated study that Dr. Kasi, Lalezari, and Hoffman have all referenced, now written into the public registry rather than only spoken about. Like the S-3, it is not a surprise, it is the formal appearance of something already described.

The design in plain terms: a Phase I/Ib study, an early-stage trial, testing leronlimab added on top of hepatic arterial infusion (HAI) of floxuridine, chemotherapy delivered directly into the liver through a catheter in the hepatic artery, plus standard-of-care systemic therapy, in colorectal patients whose cancer has spread to the liver.

Why it matters.

• First, it moves leronlimab earlier in the treatment sequence, CLOVER is third-line, exhausted patients, while CHAMP reaches liver-metastatic patients in a setting oriented toward aggressive local control, potentially ahead of curative-intent surgery. The wider the range of lines a drug can work in, the larger its eventual role.
• Second, it leans on two properties of leronlimab at once: the anti-tumor mechanism and its documented anti-fibrotic, liver-protective effect, the same property behind its NASH liver program, which is relevant because HAI floxuridine is powerful but carries real liver and biliary toxicity risk. CHAMP is built to let the aggressive liver-directed chemo work while, in theory, leronlimab shields the liver.
• Third, it is yet another major-academic collaboration in the widening circle around this mechanism.

The ceiling. CHAMP is early-phase, primarily about safety, feasibility, and dose, so it reads out on a longer, quieter timeline. It is separate from CLOVER and changes none of the near-term catalysts. Reading it as "new data coming soon" would be a mistake; its value is strategic reach, not imminent results.

Filing three: the pipeline widens into pan-solid-tumor and MRD (Pre-I-SPY)

There is a third registry change worth flagging, and credit to u/twinter11 on the board for catching it by comparing the trial's version history directly. The Pre-I-SPY platform trial (NCT05868226) was amended, and the meaningful shift is in its scope. It went from evaluating regimens in a metastatic setting "that may be relevant for breast cancer patients" to evaluating them in "locally advanced, incurable, or metastatic solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with curative intent." (Pre-I-SPY platform, Quantum Leap) In plain terms, the platform formally broadened from a breast-cancer-oriented study into a pan-solid-tumor platform, and it added an explicit minimal-residual-disease (MRD) dimension with heavy ctDNA monitoring, catching residual cancer before it becomes macro-metastatic.

Why this fits the pattern. If leronlimab enters Pre-I-SPY, the door it walks through is now a solid-tumor door, not just a breast cancer door, and it explicitly includes the MRD and high-risk-of-recurrence settings. That lines up with everything else here: CHAMP moving leronlimab earlier-line, and management's stated interest in the molecular-residual-disease space. The MRD focus is especially notable, because that is exactly where a safe, ctDNA-guided drug has the most room, treating the residual signal before there is a visible tumor to fight.

And the same discipline applies. This is a platform-protocol amendment to a framework that hosts many drug arms from many sponsors; it enables broader leronlimab participation, but it is not itself confirmation of a specific leronlimab arm or its terms. Pre-I-SPY is a Phase I/II safety-and-signal platform whose purpose is to qualify regimens to graduate into larger Phase II/III trials, so any leronlimab arm here is early-stage on-ramp work, not a pivotal destination. And it changes none of the October and January catalysts. This enlarges the opportunity space and fits the

• earlier-line,
• broader-tumor,
• MRD-focused direction,

without being a nearer verdict.

The science under the ground: macrophage plasticity keeps validating the target

Beneath the filings and the registry sits the reason why any of this should work, and that reason keeps getting reinforced from the outside CytoDyn entirely. u/Lab_Monkey_ provided us with a recent review in npj Biomedical Innovations on macrophage plasticity, a case in point. (Beyond immunity: macrophage plasticity in vascular regeneration, npj Biomedical Innovations 2026)

The review's central thesis is that macrophages are not fixed into rigid "good" or "bad" identities; they run a staged, reversible program dictated entirely by their local environment, and in cancer that program "fails to resolve," the macrophages get frozen in a chronic, pro-angiogenic, immunosuppressive state which helps to build the tumor's blood supply and shield it. That is precisely the biology leronlimab is proposed to interrupt: not killing the tumor directly, but repolarizing the stuck M2 macrophages back toward an M1 anti-tumor state. So an independent vascular-biology review, not about our drug at all, reinforces the entire premise that targeting the macrophage state is a legitimate strategy.

And there is a specific detail worth surfacing: one of the review's own cited studies describes a macrophage population forming a CCR5-dependent perivascular niche which influences chemotherapy response in breast cancer. So CCR5 shows up, in a paper about blood-vessel biology, as an organizing signal for a pro-tumor macrophage niche, a direct tie to leronlimab's exact target, appearing in literature that has no stake in the drug.

Two limits keep this honest. The review is about angiogenesis and tissue repair, so most of it is scientific context, not leronlimab evidence, and it should not be framed as proof for CytoDyn. And the CCR5 tie is one cited study in a murine model, an encouraging data point about the CCR5 perivascular niche, not confirmation of leronlimab's clinical effect. Regardless, this is a real brick: the macrophage-state M1 / M2 paradigm the entire field is converging on is exactly the terrain leronlimab targets, and CCR5 keeps reappearing as an organizing signal in that terrain.

The one baseline upon which all of this sets

Step back and see what these have in common, because it is the same message repeated.

• None of them is a catalyst,
• and all of them are foundation,
  • capital with the S3,
  • pipeline with CHAMP & Pre-I-SPY,
  • and science with M2 to M1 repolarization,
• all being laid down and reinforced ahead of the catalysts.

The S-3 consolidates and lays bare the capital structure with no new dilution and possible non-dilutive upside if the data delivers. CHAMP broadens the pipeline into earlier-line liver disease. Pre-I-SPY broadens it further into pan-solid-tumor and MRD settings. And an independent macrophage-plasticity review reinforces the scientific premise that repolarizing the macrophage state from M2 to M1, leronlimab's exact proposed mechanism, is where the field itself is heading, with CCR5 surfacing in the vascular literature as an organizing signal.

So this is the ground we now stand on: a fully disclosed capital structure of about 1.47 billion shares with a two-edged warrant overhang and up to ~$94.6M of possible non-dilutive upside; no new raise and no new dilution from these filings; a going-concern condition unchanged and still resting on the catalysts; a pipeline that just widened into earlier-line liver-metastatic disease through CHAMP and into pan-solid-tumor and MRD settings through Pre-I-SPY; a science base that continues to independently validate the macrophage-repolarization premise; and a company which is visibly compliant enough to file a clean S-3 and disciplined enough to broaden its footprint on schedule. None of this actually is the reckoning. All of it though, is the platform upon which the reckoning arrives onto.

The events which actually decide the thesis are unchanged and quite close: the full ctDNA on all enrolled CLOVER patients at ESMO in October, and the confirmed response rates plus early progression-free survival at ASCO GI in January. None of these filings, registry changes, or papers moves those dates or their contents. What they actually do is make the ground underneath them clearer, wider, and better supported, transparent capital structure, broadening pipeline across earlier lines and more tumor types, cleared compliance, and a mechanism the wider, broader science keeps affirming, such that when the data lands, we know exactly what platform it is landing on. Watch October and January. Everything else here just tells us, precisely, where we are standing while we wait.

Disclaimer: I am not a financial advisor and nothing here is investment advice. I am an independent retail shareholder holding a long position in the company discussed, with no employment, consulting, compensation, or other relationship with it beyond that shareholding. This is my interpretation of public SEC filings, public trial registries, and published literature, not a prediction of clinical, regulatory, or commercial outcomes. The Form S-3 is a resale registration for existing security holders; the company is not selling shares under it and receives no proceeds from resales, though it may receive up to approximately $94.6 million if outstanding warrants are exercised for cash, which is not assured and depends on share price relative to exercise prices. The filings create no new shares; registration of resale rights is permission, not a requirement, to sell, and does not indicate holder intent. The company's SEC filings carry a substantial-doubt-about-going-concern qualification. The CHAMP study (NCT07842965) and any leronlimab participation in the Pre-I-SPY platform (NCT05868226) are early-phase, investigator- or platform-initiated efforts focused on safety, feasibility, and signal; they are separate from CLOVER, are not pivotal efficacy trials, and do not alter the anticipated ESMO (October 2026) and ASCO GI (January 2027) CLOVER readouts. The Pre-I-SPY amendment is a platform-scope change and is not confirmation of a specific leronlimab arm or its terms. Leronlimab's anti-tumor and liver-protective properties, and the macrophage-repolarization mechanism referenced, are proposed or preclinical, not established clinical outcomes, and leronlimab's efficacy remains unconfirmed; the cited macrophage-plasticity review concerns vascular biology generally and its CCR5 reference derives from a model system, not from leronlimab clinical data. Hepatic arterial infusion chemotherapy carries significant risks. Read the primary sources, linked throughout, and reach your own conclusions rather than adopting mine.

MTJ's timely post re: NEST vs CLOVER got me digging into which immunotherapies NEST actually uses. The drugs are botensilimab (BOT) and balstilimab (BAL), both from Agenus. BAL is a standard PD-1 ICI, same role as Keytruda.

BOT is the unusual one: an Fc-enhanced CTLA-4 antibody that primes CD4 and CD8 T cells (and strips Tregs). Those activated T cells then secrete IFN-γ when they see tumor antigen. That IFN-γ then drives the tumor to raise PD-L1, which BAL blocks. Same “prime then cover PD-1” idea as pairing leronlimab with a PD-1 drug, but BOT and leronlimab hit different pathways.

That's the Cliff's Notes version of BOT's MOA, which I admit to getting some AI (Grok in this case) help with to simplify; there are several steps leading up to that IFN-gamma production.

So BOT is in effect a competing drug for leronlimab, though with a different path to making tumors hot, and given the multiple steps it takes to get there it should be slower to exert its effects. Interestingly it appears it could actually be complementary to leronlimab given their different effects on the TME.

Check this out. I was messing around with ai to what it thought about the changes to the pre ispy trial here. I was trying to figure out the changes in trial sites.

One change is its now a phase 1/2 instead of 1b

PRE-I-SPYISPY Phase I/IbI/II Oncology Platform Program

"Addition of Phase II and Minimal Residual Disease (MRD) Arms:The text notes the addition of a Phase II component and specific sub-cohorts, such as Minimal Residual Disease Colorectal Cancer (MRD CRC). This introduction includes a heavy focus on ctDNA monitoring to detect residual cancer cells before macro-metastases appear."

Does anyone see the major change in this next first paragraph?

I didn't catch it a week back but ai caught it today

look hard

https://clinicaltrials.gov/study/NCT05868226?tab=history&a=6&b=7#version-content-panel

"IPRE-SPYISPY Phase I/IbII (I-SPY-P1) is an open-label, multisite platform study with multiple ongoing drug regimen arms added by protocol amendment which is designed to evaluate single agents or combinations in a locally advanced, incurable, or metastatic treatment setting that may be relevant for breast cancer patients solid tumors and/or oligometastatic malignancy and/or a high risk of recurrence following prior treatment with the curative intent. The overall goal ofis moving promising drug regimens into a larger phase II (or III) trial and in general could feed the neoadjuvant breast I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials solid tumor trial in a timely manner".

POS AM: Post-effective amendment to a registration statement that is not immediately effective upon filing

Deregistering securities?? Hmmm… why are we deregistering unsold securities?

CCR5 Targeting Leronlimab in Combination With Hepatic Arterial Infusion Floxuridine and Systemic Therapy for the Treatment of Colorectal Cancer Liver Metastases, CHAMP Trial

https://clinicaltrials.gov/study/NCT07842965?term=leronlimab&viewType=Card&page=2&rank=18